Endoplasmic reticulum stress response is involved in Mycobacterium tuberculosis protein ESAT-6-mediated apoptosis

FEBS Lett. 2010 Jun 3;584(11):2445-54. doi: 10.1016/j.febslet.2010.04.050. Epub 2010 Apr 21.


Mycobacterium tuberculosis (Mtb) infection leads to the induction of the apoptotic response, which is associated with bacilli killing. The early secreted mycobacterial antigen ESAT-6 of Mtb has been shown to induce apoptosis in human macrophages and epithelial cells. In the present study, we demonstrate that the stimulation of human epithelial A549 cells by ESAT-6 induces the endoplasmic reticulum (ER) stress response. We observed that ESAT-6 treatment increases intracellular Ca(2+) concentration, which results in ROS accumulation, and therefore induces the onset of ER stress-induced apoptosis. Our results uncover a novel apoptotic mechanism of ESAT-6 through ER stress responses in pathologic conditions such as tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Bacterial / metabolism*
  • Apoptosis*
  • Bacterial Proteins / metabolism*
  • Endoplasmic Reticulum / metabolism*
  • Humans
  • Macrophages / metabolism
  • Mycobacterium tuberculosis / metabolism*
  • Proteins / metabolism*
  • Reactive Oxygen Species / metabolism
  • Tuberculosis / metabolism


  • Antigens, Bacterial
  • Bacterial Proteins
  • ESAT-6 protein, Mycobacterium tuberculosis
  • Proteins
  • Reactive Oxygen Species